The overall objective of this project is to elucidate the pathogenesis of neonatal hypoglycemia. Our previous studies had indicated that newborn infants are uniquely susceptible to developing hypoglycemia during fasting, because of limited capacities for both ketone synthesis and gluconeogenesis. Studies of both small-for-gestational-age and normal, term infants revealed that higher levels of plasma glucose are maintained when fasting stress is minimized by starting feedings within two hours of delivery. In addition, during the past year, it was found that maternal hyperglycemia induced by the use of glucose-containing intravenous fluids during elective caesarina section was associated with low levels of plasma glucose in neonates at two hours of age. These observations of major effects of pre and postnatal variables on plamsa glucose levels in infants on the first day of life raise important questions about the current practice of defining neonatal hypoglycemia on a statistical basis. Studies of the development of capacity for ketone synthesis are in progress both in-vivo in term infants and in vitro in liver homogenates from newborn guinea pigs. These studies will be continued during the current year to define the locus of limitation in capacity for ketone synthesis at birth and the factors involved in the development of this pathway.